This invention relates generally to catheters for use in delivery of drug, particularly in the context of site-specific drug delivery.
Many diseases or indications require long term, chronic delivery of drugs or agents to a patient, e.g., cancer, arthritis, heart disease, etc. Long term delivery of drugs or agents can be accomplished by use of drug delivery systems comprising drug delivery devices which may be implanted in a patient""s body or retained externally. Drug delivery systems can also deliver drugs or agents to a targeted site within the body via catheters attached to drug delivery devices with the distal end of such catheters placed at the desired site of delivery in the body, with the catheter acting a conduit for the drug or desired agent from the drug delivery device to the desired site of delivery in the body. Drug delivery devices which have adjustable drug delivery rates are known in the art (see, e.g., U.S. Pat. No. 4,692,147). However, such devices with variable or programmable drug delivery rates often include complex mechanical elements which may make such drug delivery devices bulky and subject to failure. Constant drug delivery devices provide for delivery of drug at a pre-selected, substantially non-fluctuating rate, thus providing for predictability of the dose delivered. However, constant drug delivery devices have the limitation that the rate of drug or agent delivered cannot be readily adjusted, particularly where the drug delivery device is implanted in the body. The ability to readily alter the rate at which drug is administered is often desirable in that it provides flexibility in a therapeutic regimen, and in certain cases, may be a requirement in certain therapies. For example, the drug requirements of a patient may not be ascertainable prior to the commencement of a therapy (e.g., dose titration may be required to determine appropriate dosage), or a patient may require increasing doses (e.g., due to development of tolerance) or decreasing doses (e.g., as the patient gets well). In a constant drug delivery device, adjusting the rate of drug delivery can require the removal of the device from the body of a patient and/or detachment from a drug delivery system (e.g., detachment from a catheter) and adjustment or even replacement of the device.
There is thus a need in the field for a mechanism which allows for adjustment of the rate of a drug delivery device yet obviates the need for complex or bulky regulatory elements associated with the drug delivery device. The present invention addresses this problem.
The present invention features methods and devices for modulating the rate of delivery of a drug formulation from a drug delivery device by diverting drug away from a drug delivery pathway. In one embodiment, a flow regulator is positioned relative to a drug delivery pathway of a drug delivery system so that adjustment of the flow regulator can provide for diversion of drug away from the drug delivery pathway. Diverted drug can be either delivered into the systemic circulation of the subject, or can be captured in a waste reservoir.
In one aspect the invention features a flow regulator comprising a delivery conduit defining a proximal delivery inlet, a distal delivery outlet, and a delivery lumen extending between the proximal delivery inlet and the distal delivery outlet, the delivery conduit lumen defining a delivery pathway; and a diversion element positioned at the diversion inlet so as to facilitate diversion of flow of drug away from the delivery pathway.
In another embodiment, the flow regulator further comprises a diversion conduit defining a diversion inlet, a diversion outlet, and a diversion lumen extending between the diversion inlet and diversion outlet, the diversion conduit lumen defining a diversion pathway, wherein the diversion inlet is in fluid communication with the delivery conduit lumen. In this latter embodiment, drug is diverted from the delivery pathway and into the diversion pathway defined by the diversion conduit.
In another aspect the invention features a drug delivery system comprising a flow regulator and a drug delivery device, and optionally a drug delivery catheter.
In another aspect the invention features methods for administering drug to a subject and for controlling an amount of drug administered to a subject using the flow regulator of the invention.
A primary object of the invention is to provide a device and method for adjustment of the rate at which drug is delivered from a drug delivery device.
Another advantage of the invention is that the control of drug delivery from a drug delivery device to a treatment site is accomplished without the need for adjustment of any element the drug delivery device per se, e.g., without adjusting the volume rate of delivery generated by a drug delivery device. This is particularly advantageous where there may be particular difficulties or inconveniences in adjusting the amount of drug delivered from the drug delivery device.
Another important advantage of the invention is that the devices of the invention can be used in a manner that avoids the need to perform invasive procedures to adjust the dose delivered from a drug delivery device. For example, the flow regulator can be provided such that the diversion element of the flow regulator remains accessible outside the subject""s body. Alternatively, the diversion element can be remotely controllable, thus allowing for adjustment of the implanted flow regulator from outside the body.
The invention is also advantageous for use where microquantities of drug are to be delivered to a treatment site, where the treatment site is a relatively confined space, and/or where the drug delivery is site-specific. In these contexts, diversion of even a small volume of drug can elicit a proportionately greater effect upon the total volume of drug delivered to the treatment site and/or the biological effect at the treatment site.
Another advantage of the invention is that where the invention is used in connection with delivery of drug to a specific treatment site. The diverted, waste drug can be dumped into the systemic circulation, where the drug is rapidly metabolized, inactivated, and/or eliminated and thus has no substantial systemic effect upon the subject. Only drug delivered to a specific treatment site has the desired biological effect. Thus the invention can be particularly attractive where the delivery of a therapeutically effective amount of drug can be accomplished through delivery at a relatively low volume rate (e.g., from about 0.01 xcexcl/day to about 200 xcexcl/day, usually about 0.04 xcexcl/day to about 20 xcexcl/day, more usually about 0.1 xcexcl/day to about 8.0 xcexcl/day) or in microquantities, where only a very small amount of drug need be diverted to provide for adjustment of dose delivered to a specific treatment site.